PCSK9 inhibition as the new hope for patients with familial hypercholesterolemia, statin intolerance and eventually for those at the highest cardiovascular risk? Focused on alirocumab, Praluent(R)
Abstract
At the present time there are novel hypolipidemics registered globally (alirocumab was the first drug of this group in the world registered by an American drug agency FDA) and in Europe, which in many ways differ from the medicines administered until now. They are bringing another advancement in the treatment of disorders of lipid metabolism and in preventive cardiology.
Alirocumab is a fully human monoclonal antibody to PCSK-9 enzyme (proprotein convertase subtilisin kexin-9). PCSK-9 enzyme plays an important role in the metabolism of LDL-cholesterol through affecting the breakdown and eventually the amount and activity of LDL-receptors.
From the clinical point of view it is essential that drugs from this group are administered parenterally, as a subcutaneous injection. In the case of Praluent(R) the interval between administration is two weeks.
The dose is then 75 or 150mg in a 1ml injection. From the clinical point of view it is particularly important that alirocumab decreases LDL-C concentrations by 50-60%, it decreases Lp/a/ levels by 25-30%, and it also positively influences other components of lipid metabolism and, above all, is very likely to have a potential to decrease a cardiovascular risk.
Although the resuIts of morbidity and mortality studies are expected in the coming years, initial analyses strongly indicate a clinically significant reduction of CV events. Alirocumab, Praluent can be administered as monotherapy (mainly to statin-intolerant patients), however it will be primarily administered in combination with the other hypolipidemic drugs (in particular statins) where the effort to reach target values has not succeeded.